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Unusual Nucleophilic Addition of Grignard Reagents in the Synthesis of 4-Amino-pyrimidines.

ABSTRACT: Pyrimidines have always received considerable attention because of their importance in synthesis and elucidation of biochemical roles, in particular that of vitamin B1. Herein, we describe a reaction pathway in a Grignard reagent-based synthesis of substituted pyrimidines. A general synthesis of ?-keto-2-methyl-4-amino pyrimidines and their C6-substituted analogues from 4-amino-5-cyano-2-methylpyrimidine is reported. The presence of the nitrile substituent in the starting material also results in an unusual reaction pathway leading to C6-substituted 1,2-dihydropyrimidines. Grignard reagents that give normal pyrimidine products under standard reaction conditions can be switched to give dihydropyrimidines by holding the reaction at 0 °C before quenching.

SUBMITTER: Tinson RAJ

PROVIDER: S-EPMC6644423 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Unusual Nucleophilic Addition of Grignard Reagents in the Synthesis of 4-Amino-pyrimidines.

Tinson Ryan A J RAJ Hughes David L DL Ward Leanne L Stephenson G Richard GR

ACS omega 20180810 8

Pyrimidines have always received considerable attention because of their importance in synthesis and elucidation of biochemical roles, in particular that of vitamin B1. Herein, we describe a reaction pathway in a Grignard reagent-based synthesis of substituted pyrimidines. A general synthesis of α-keto-2-methyl-4-amino pyrimidines and their C6-substituted analogues from 4-amino-5-cyano-2-methylpyrimidine is reported. The presence of the nitrile substituent in the starting material also results i ...[more]

PMID: 31459026

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